With the expanding legalisation of the medical and recreational use of cannabinoids there is an urgent need for a simple and effective process that isolates these cannabinoids from their raw material, marihuana. This process should have a high extraction yield and provide cannabinoid products with a purity that meets pharmaceutical standards.
Several processes have been developed to isolate pure cannabinoids from marihuana. U.S. Pat. No. 8,895,078 discloses a process using supercritical carbon dioxide as the extraction solvent. However, this solvent also extracts waxes, terpenes, glyceride oils, phosphatides and colouring compounds from the marihuana so that the extract requires extensive purification, which purification inevitably leads to loss of cannabinoids.
The extraction process disclosed in WO 2004/026857 uses ethanol or hexane as extraction solvent. Both solvents are inflammable and thus require an X-proof extraction facility which increases the investment required and the extract also requires purification. Such a purification process has been disclosed in CA 2,872,528, which process comprises thin film evaporation of the extract followed by flash chromatography of the distillate. The equipment concerned implies that the process can only be carried out at laboratory scale. That also holds for the centrifugal partition chromatographical method described in the doctoral thesis of Arno Hazekamp (Leiden, 2007).
In a more recent patent application (US 2015/0126754), a high purity Δ9-tetrahydrocannabinol (THC) isolate is produced from a crude solvent extract by subjecting this extract to thin film evaporation, chromatographically fractionating the refined extract to obtain high purity fractions and subjecting the high purity fractions to another thin film evaporation. Again, the process comprises many steps and is only suitable for small scale preparations. An extraction process using multiple solvents has been disclosed in US Patent Application Publication US 2016/0326130. Marihuana flowers are first of all extracted with a non-polar organic solvent wherein the yield is approximately 50-70% with respect to the main cannabinoids. Then the organic extract is extracted with an aqueous base and subsequently, multiple extractions with tert-butyl methyl ether, washing with water, extraction with pentane, treatment of the pentane miscella with activated carbon are necessary to arrive at a purified Δ9-tetrahydrocannabinol product. It uses large amounts of solvents and thereby generates large amounts of waste and effluents.
WO 2017/026897 A1 discloses a laboratory extractor for contacting marihuana with the extraction solvent ethanol. US Patent Application Publication US 2017/0008870 discloses a process to extract marihuana with a solvent and cooling the solvent extract so that a precipitate is formed and removing the precipitate by filtration. By further cooling to temperatures as low as −50° C. or even −85° C., a cannabinoid precipitate is formed that is collected. In the example, two 300 mL cans of butane are used to extract only 50 g of Cannabis plant material which may contain only 5 g of cannabinoids, which makes it an expensive process.
Another process for the isolation of cannabinoids from marihuana has been disclosed in U.S. Pat. No. 7,622,140. In this process the cannabinoids are volatilized by contacting the Cannabis plant material with a gas that has been heated to a temperature above 100° C. that is sufficiently high to volatilize at least one cannabinoid but not so high as to cause pyrolysis of the Cannabis plant material, and condensing the vapour and collecting the condensate.
In summary, current processes to isolate cannabinoids from their raw material (marihuana) comprise a large number of steps: harvesting the trichomes from the female plants, comminuting the trichomes, drying the comminuted trichomes, extracting the dried plant material with a solvent like supercritical carbon dioxide, collecting the extract, dissolving the extract in ethanol and cooling it so as to precipitate the waxes, removing the waxes by filtration, treating the alcoholic filtrate with activated carbon to remove colouring compounds, removing this carbon adsorbent by filtration, and finally, evaporating the alcoholic solution to dryness. This leads to a mixture of cannabinoids the composition of which reflects the raw material and if these were to be decarboxylated and/or separated that would entail further processing steps. Besides, each step leads to a yield loss and given the selling price of purified cannabinoids, this constitutes a serious disadvantage. Moreover, current processes operate at laboratory scale which means that there is a need for a simple process that isolates cannabinoids from Cannabis plant material in high yield and that can be executed at a sufficiently large scale to meet market demands.